Project Background/Rationale: Traumatic brain injury (TBI), even mild TBI/concussion, is known to be associated with Alzheimer's disease and other progressive neurological disorders in both Veteran and non- Veteran populations. The VA cares for a large number of Veterans who have incurred TBI. Many of these Veterans are also treated inside and outside the VA for comorbid pain and mental health disorders, often with opioid and other psychotropic medications. These medications may contribute to the risk of adverse neurological outcomes. Although the VA has reduced opioid prescribing in recent years, many Veterans with TBI continue to receive these medications from providers both inside and outside the VA. In the post-9/11 combat era, in which TBI has been deemed the ?signature? injury of war, and in the context of the US opioid epidemic, research is needed to examine the effects of opioids and other psychotropic medication use on the long-term neurological outcomes of Veterans with TBI history. Longitudinal approaches using VA administrative data and clinical research will both contribute to this field of study. However, these approaches are hampered by important methodological limitations. First, although VA administrative data (i.e. medical records) are a powerful source of information on health diagnoses, healthcare utilization, and prescription dispensation for the millions of Veterans who use VA healthcare annually, the validity of using TBI-related diagnosis codes in administrative data to identify Veterans with TBI is questionable. And second, although clinical studies have been designed specifically to examine the causal effects of TBI on neurological outcomes, these studies may lack complete data (i.e., VA and non-VA) on Veterans' psychotropic medication exposures. Research examining the validity of TBI-related diagnosis codes, and methods to collect Veterans' complete medication exposures, will help advance this field significantly. Project Aims: This project will develop best practices for epidemiologic and clinical research, and serve as the foundation for a new research program, that evaluates the impact of opioids and other psychotropic medications on the long-term neurological outcomes of Veterans with TBI history. The specific aims are to: (1) Identify valid approaches for identifying Veterans with TBI in VA administrative data; and (2) Develop methods to measure Veterans' complete opioid and other psychotropic medication exposures in clinical research examining the effects of these medications on long-term outcomes of Veterans with TBI. Project Methods: The proposed 2-year project will generate the methods and preliminary data needed for subsequent research focused on opioids and neurological health among Veterans with TBI. This project will use VA administrative data (Aims 1 and 2), and state prescription drug monitoring program (PDMP) data (Aim 2), to develop reproducible and scalable approaches to valid TBI and medication measurement. For Aim 1, the validity of International Classification of Diseases ? 10th Revision ? Clinical Modification (ICD-10-CM) diagnosis codes for TBI research will be analyzed using the VA's comprehensive TBI evaluation data as a criterion standard. The concordance, sensitivity, and specificity of ICD-10-CM coding algorithms will be estimated for identifying ?true? TBI cases and for distinguishing between levels of TBI severity. For Aim 2, VA administrative data will be linked with data from Oregon's PDMP to capture complete prescription histories among Veterans in Oregon. Linked VA/non-VA data will be used to examine the completeness and validity of using the VA-only sources of prescription data that are more readily accessible ? across states ? for VA clinical research. Anticipated Impact: This SPiRE will serve as a necessary first step in research examining the long-term effects of opioids and other psychotropic medications on neurological outcomes of Veterans with TBI. The work we propose will inform ours and others' research studies that, over time, will help describe and address the multitude of factors affecting the neurological health of this large cohort of VA patients.